(Revised 4/8/03) Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss among elderly individuals. Treatment is available for only a small percentage of patients with the neovascular form of AMD and predictive systemic factors have not been identified. Systemic biomarkers shown to protect or increase risk in other age-related disorders have been shown either to play some role in the eye and/or retina, or there is strong biologic plausibility of a role based on available evidence. We will test the hypotheses that certain biological factors shown to be associated with oxidative processes, inflammation and/or vascular disease are associated with AMD. The overall hypothesis is that clinical manifestations of AMD are related to local and systemic biological factors, which may be influenced by modifiable environmental and/or genetic factors. We propose to examine these biomarkers with available assays in 912 subjects (59% female, 41% male): 5% of subjects with no AMD, 25% of subjects with mild AMD, 45 % of subjects with moderate AMD and 25% of subjects with advanced AMD in one eye only, all of whom provided a fasting blood specimen in 1996 (over 90%) or 1997. Subjects will be followed prospectively for at least seven years. This study is an approved ancillary investigation of the Age-Related Eye Disease Study (AREDS), which is designed to assess the incidence, progression and risk factors for AMD and cataract and includes a randomized trial to assess the effects of antioxidant vitamins and minerals on these diseases. AREDS provides a unique opportunity to test these associations efficiently and prospectively. This is likely the largest available cohort of patients with various stages of AMD who have been well characterized in terms of AMD and other potential risk factors. The long-term goal is to provide insight into the pathogenesis of AMD and to identify modifiable risk or protective factors that may lead to preventive measures and improved therapies for this common cause of visual loss in the elderly.